The
study's two principal conclusions are 1) Medical radiation,
introduced into medicine in 1896, became and remains a necessary causal
co-actor in over half of the fatal cases of cancer in the USA, and 2)
became and remains a necessary causal co-actor also in over half of the
fatal cases of ischemic heart disease (coronary artery disease) in the USA.

From
these conclusions plus the fact that x-ray harm is
approximately proportional to accumulated x-ray dose, it follows that a
very great deal of future cancer and ischemic heart disease (IHD) could be
prevented by reducing the dose-levels customarily administered during
x-ray imaging procedures, especially CT and fluoroscopy. Indeed, it is
very often feasible to get good images with half (or less) of the customary
dose. Doing so could prevent about 250,000 premature deaths every year
in the USA, by our estimate.

The
conclusions above are obviously so important for human
health that they demand thoughtful, independent scrutiny, i.e.,
peer-review.

Part 2 What Has Peer-Review Produced So Far?

How
have our conclusions held up under peer-review? Has
someone shown a reason to discard them, to ignore them, or to modify
them? Not so far.

Valid
critiques are often of two types: A demonstration that a
better explanation exists for the same observations
(Gofman 1999 Chapter
68), and/or a demonstration that the new conclusion is "impossible"
because it contradicts some other conclusion of a scientifically
incontrovertible nature (Gofman 1999 Chapter 67).

So
far, no critique has produced such a demonstration, as will be
seen below when we summarize the six main critiques. (This document
omits the favorable comments, due to space limits.)

Why,
then, are the findings not yet treated as one of the major
medical breakthroughs of the past decade? Experience shows that it always
takes time for humans to discard mistaken beliefs, especially when the
beliefs are so comforting (e.g., "The harm from medical x-rays is trivial").
Still, patience may be no virtue when very many premature deaths could be
prevented by a little speed
(Gofman 1999pp.17-20). We agree with the
author, Kenneth Graham, who has observed:

"The
strongest human instinct is to impart information, and the
second strongest is to resist it."

Part 3 Orientation: Why Our Study Was Done

In
order to understand the six critiques at issue, one must have at
least an overview of why and how the 1999 study was done. The starting
point is that ionizing radiations, including x-rays, have been an established
cause of human cancer for decades
(affirmation in IARC 2000).

One
important reason for our doubting the credibility of the 1%
to 4% estimates is that they were derived from an estimate of average per
capita x-ray dose in the USA. As a result of doing our earlier study of
radiation-induced breast cancer
(Gofman 1996), we learned that there is no
way for anyone to make a reliable estimate of what the average per capita
accumulated dose in the USA was --- or is today --- from pre-cancer
medical x-rays.

Past
x-ray exposures cannot be ignored. Some 45 years after the
1945 exposure to A-bomb radiation, the Hiroshima-Nagasaki survivors are
still producing excess cancer in a dose-dependent fashion
(Pierce 1996
p.6). Some mutations induced by ionizing radiation persist in a
dose-dependent fashion for decades
(Lucas 1992 Figure 6;
Kodama 1993),
probably for the remaining lifespan. X-rays received 50 years ago or
earlier can and do contribute to today's cancer mortality.

The Absence of Measured X-Ray Doses

Although
x-rays have been widely used in medical practice for
over 100 years, in no decade have x-ray doses been measured --- indeed,
for about the first 40 years, the response of the skin was the only
"measure."

Even
after measurement became technically possible, it was not
done in practice --- and is very rarely done today. We venture to assert
that there is no one in the USA who knows or could find out what his/her
accumulated dose of pre-cancer x-rays is to any part of the body (e.g.,
breasts, testes, lung, heart).

From
one type of procedure to another, the x-ray dose can vary
by 100-fold. There are only very loose estimates of how many procedures
of which type were given in any decade. A leading figure in radiology,
Henry D. Royal, M.D., estimates that average per capita x-ray doses are
2 or 3 times higher now than they were in 1980, due to expanded use of
CT (in Veterans 2000 pp.260-261).

Moreover,
even for the same procedure, on patients of the same
size, sporadic sampling programs show that x-ray doses vary widely from
facility to facility, and even within a single facility.

The Scientific Challenge

Given
the lack of dose data about x-rays in the USA, we
consider the widely used average per capita dose-estimates --- past and
present --- to rest on "thin air." A colleague of ours commented, "Well,
you have undertaken an inquiry where there will never be any data!"

So,
our scientific challenge was to try designing a study which
could produce a scientifically better estimate of the impact of pre-cancer
x-rays on cancer mortality, by entirely avoiding the very flimsy ("thin air")
dose-estimates --- and by avoiding also the consequently unreliable
estimates of risk per dose-unit.

Part 4 Orientation: How Our Study Was Done

Instead
of using any dose-estimates, we used the premise that
average per capita dose per 100,000 population is approximately
proportional to the number of practicing physicians per 100,000 population
(physician density) --- supporting evidence in
Mettler 1987 p.134 ---
because physicians order x-rays even when others perform them. Thus the
relative magnitude of physician-density values in the nation's nine
permanent Census Divisions should reflect the relative magnitude of
the per capita x-ray dose delivered in each Census Division. The earliest
year is 1921 for which we obtained the density data for all nine Census
Divisions (Pennell 1952;
later decades, see AMA).

Our
design was to see if any correlation (dose-response) exists
between magnitude of physician density and magnitude of age-adjusted
cancer mortality rates, by Census Divisions. Nine Divisions make each test
a nine-point correlation.

The
year 1940 marks the first decade for which every state
reported mortality data for all major causes of death, including cancers
(Grove 1968;
later decades, see Natl. Center). The
main reason for doing the analysis by Census Divisions (not
counties or states) is to minimize degradation by migration.
Prior to World War Two, there was far less migration from
one Census Division to another than after 1940. To a first
approximation, people accumulated their x-ray doses over a lifetime in the
same Census Division where they died. The number of states per Division
ranges from 3 to 8.

Our
dose-response study would not have been possible, however,
if the rank order of physician-density values had switched so much over
time that the population in every Census Division accumulated about the
same average x-ray dose. But it turns out that the rank order
of the nine Census Divisions, with respect to physician density, has
been remarkably stable (Gofman 1999p.66) ---
stable enough that you can predict the national age-adjusted cancer
mortality rates (male, female) rather well for 1940 by examining
relative physician density by Census Divisions in 1921, 1931, and 1938
(Gofman 1999 p.214, p.222; for IHD in 1950, see p.296).

And
so we undertook a mammoth dose-response study, enrolling
the entire US population (131.7 million people in 1940).

Eleven
of the 12 cancer studies produced statistically significant,
positive dose-responses between physician-density and age-adjusted cancer
mortality rates in 1940; only female genital cancers showed no relationship
with physician density. In all other tests, as physician density rose, so did
the age-adjusted cancer mortality rates. Indeed, the correlation was so
nearly perfect in 8 of the 11 tests that the R-squared values ranged from
0.86 to 0.96; in the other 3 tests, R-squared values ranged from 0.72 to
0.78 (all tabulated in Gofman 1999 p.217).

The
11 strong correlations permitted us to estimate the impact of
medical radiation upon 1940 cancer mortality --- without using any "thin
air" dose estimates or any unreliable values for risk per unit dose.

How?
We extended each correlation's "line of best fit" down to
zero physician density (no medical x-rays), and thus we obtained the
estimates of what the cancer mortality rates would most probably have been
in the absence of accumulated exposure to medical x-rays.

Results of Twenty-Eight Noncancer Dose-Response Tests

To
our astonishment, one of the noncancer entities --- ischemic
heart disease (IHD) --- produced spectacularly strong and positive
dose-responses between physician density and age-adjusted mortality rates
in 1950 (the first decade in which all states reported mortality data for
IHD). For males, the R-squared value was 0.95; for females, 0.83
(Gofman 1999 Chapters
40, 41). And again, we could estimate the impact
of x-rays on IHD-causation by extending the best-fit line to zero
physician density (no medical radiation).

All
the other noncancer dose-responses (Chaps. 24-37) were
either negative --- higher physician density going with lower death rates
--- or flat, with the only exceptions being male and female diabetes (see
explanation, Gofman 1999 p.247)
and, male G.I. ulcers (barely statistically
significant; see comment in Gofman 1999 bottom of
p.22).

Combined,
all noncancer nonIHD causes of death had a
statistically very significant negative correlation with physician density ---
in great contrast with the very strong positive correlations for cancer and
for IHD with physician density.

Part 6 First Critique: Correlation vs. Causation

One
of the first critiques we received belongs to the "maybe there
is a better explanation" class. It comes from Arthur C. Upton, M.D.,
former director of the National Cancer Institute (1977-1979), member of
all the main radiation committees, including the National Research
Council's Committee on the Biological Effects of Ionizing Radiation, 1972,
1980, 1990 (chair). We quote his critique
(Upton 1999) in its entirety:

"Dear
Dr. Gofman: Thank you for kindly sending me a copy of
your recent book entitled `Radiation from Medical Procedures in the
Pathogenesis of Cancer and Ischemic Heart Disease.'

"Your
observations are impressive and are consistent with the
linear-nonthreshold dose-response hypothesis for the genetic and
carcinogenic effects of ionizing radiation, and they support the wisdom of
the ALARA principle [As Low As Reasonably Achievable] in radiation
protection.

"At
the same time, however, the associations you have so skillfully
demonstrated cannot be taken as proof of causal relationships, owing to the
possible influence of confounding variables. Just as the inverse relationship
between lung cancer rates and county residential radon levels, as reported
by Bernard Cohen, does not suffice to prove that low-level exposure to
radon protects against lung cancer, neither do your observations suffice to
establish medical radiation as a causal factor in the associations you have
identified.

"Nevertheless,
I find your observations intriguing, and your
interpretation of them to be thoughtful and constructively
hypothesis-generating. I hope that your book stimulates the productive
follow-up research that your findings clearly call for. Many thanks, again,
for sharing your findings with me, and best wishes for continuing
productivity in the new millennium. Arthur C. Upton."

Our Response: Agreement on Inherent Limitations

Dr.
Upton is not suggesting that our study was designed to prove
whether or not x-rays are a cause of cancer. That was established decades
ago. Nor was our study intended to prove whether or not x-rays are a
cause of IHD. Results of our IHD tests
astonished us (Part 5, above).

Instead,
Dr. Upton is agreeing with a reality stressed repeatedly
in our study, namely that correlations are inherently unable to prove
causation, by themselves. Correlations can and do occur without being
causal.

So,
whenever a correlation is observed in biomedical research,
there is inevitably room to challenge the identity of what truly caused the
correlation to occur --- even in the widely accepted Atomic Bomb
Survivor Study, for instance. In Chapters 48 and 68 of our 1999 study, we
ourselves look for non-xray explanations of the many correlations
uncovered by our work.

Importantly,
we explore cigarette smoking as a potential
non-xray explanation. The evidence is that smoking has a negative
correlation with physician density, by Census Divisions, and so smoking
cannot be a valid cause of the observed positive correlations
(physician density with cancer and IHD mortality, by Census Divisions).

Establishing
causation in medicine is particularly difficult, not
only because of inherited biochemical individuality, but because of the
different external forces experienced by free-living humans. Before
causation is considered proven, correlations do need support from
supplemental evidence or logic, especially about a plausible biological
mechanism of causation (e.g., how xray-induced mutations could cause
IHD; see end of Note 1,
and Gofman 1999 Chapters 44, 45, 46).

The monograph, "Radiation from
Medical Procedures..." (Gofman 1999)
was sent for peer-review to Dr. Richard R. Monson, chair of the BEIR-7
Committee (the Nat'l Research Council's Com'tee on the Biological Effects
of Ionizing Radiation), with our offers (a) to supply a copy for every
member and (b) to respond to any critiques. Dr. Monson replied
(Monson 2000, 2002) that he would read the study with
interest, but that his Committee's deliberations are confidential thus affording
us at CNR no chance to respond to any critiques. The BEIR-7 Report is expected in
2003.

Part 7 Is "Urbanization" a Better Explanation?

Critique
#2. Several peer-reviewers have speculated that the
positive correlations between physician density and cancer, by Census
Divisions, may be caused by a positive correlation between "urbanization"
and physician density.

For
example, Gofman 1999 was reviewed on November 29, 2000
by the U.S. Department of Veterans Affairs, Office of Adjudication,
Veterans Advisory Committee on Environmental Hazards. The transcript
of that meeting is Veterans 2000 in our list.
Some on the Committee were highly skeptical that x-rays could be the
correct explanation. Said Theodore Colton, Sc.D., Boston University
School of Public Health:

"I
don't know what the obvious flaw is, but one of the limitations
of ecologic studies is the fact that they're very prone to confounding
variables. And it just seems to me that there's some obvious confounding
variable that affects both physicians per capita and cancer mortality that's
not being taken into account..." (Veterans 2000 p.272).

"Well,
we do know that rural versus urban, that there's a
difference in cancer rates with rates being higher in urban settings.
Certainly physicians per population is going to be weighted to those urban
settings, so that's certainly one confounding variable"
(Veterans 2000, p.274).

Our Response: What Makes City Life Carcinogenic?

Dr.
Royal and some other peer-reviewers appear to assume that
living in cities was a cancer-risk during the decades leading up to 1940
(the first year analyzed in Gofman 1999).
And they must also assume, for the
period leading up to 1940, that the more urbanized Census Divisions had
higher physician density than did rural Census Divisions. Suppose that we
share those assumptions (Gofman 1999 Chapter 68).

City
living is not itself a biological agent. But x-rays are. And
they are a proven carcinogen. According to Dr. Royal's own logic, x-rays
could explain why urban areas have higher cancer mortality rates. With
more physicians per 100,000 persons in urban areas, there are more x-rays
given per 100,000 persons --- and thus the average per capita accumulated
x-ray dose is higher in the urbanized Census Divisions than in the more
rural Divisions.

In
summary, urbanization is not a "confounding variable" in our
study. It is not a "better explanation" than x-rays for the correlations
uncovered by our work. Instead, higher exposure to medical x-rays can
provide a good explanation of why urban areas may have higher cancer
rates.

Some Tests for Validating a Speculation

It
is easy to speculate that some agent other than medical
x-rays is the true cause of the observed correlations in Gofman 1999.
After all, many proven and suspected non-xray causes exist for cancer and
IHD. However, none can provide a valid alternative to the x-ray
explanation, for the correlations uncovered in Gofman 1999, unless the
alternative can explain the observations equally well. In order to do so, an
alternative agent would have to pass all of the following tests:

Public
exposure to the non-xray agent would need a very
strong correlation with physician density, by Census Divisions.

The
correlation by Census Divisions would have to be a
positive one (not negative).

The
correlation by Census Divisions would have to persist over
time, in order to yield the predictions described
in Part 4, above.

The
non-xray agent would have to be a potent cause of nearly
every type of fatal cancer.

The
non-xray agent would have to be a potent cause of
ischemic heart disease (IHD).

The
non-xray agent would have to be not a cause of
noncancer, nonIHD causes of death. Could reviewers show evidence to
establish that "urbanization" is not a cause of noncancer, nonIHD causes
of death?

Part 8 Correlations Show Only that Doctors and Sick
People Want to Be in the Same Place?

Critique
#3. Two reviewers proposed in private communications
that maybe cancer and IHD mortality rise where physician density rises, by
Census Divisions, only because doctors and sick people want to be in the
same place. In other words, there may be a strong positive correlation
between physician density per 100,000 people and sick people per 100,000
people --- a proposition that we, too, considered
(Gofman 1999 Chap.68).

By
itself, such a correlation would be reasonable --- and
certainly consistent with the premise that where physician density is higher,
the number of x-ray procedures per 100,000 population is higher too.

Our Response: You Can't Discard the Noncancer NonIHD Facts

Because
they assume a positive correlation between physician
density and the density of sick people, by Census Divisions, these two
reviewers think "of course" mortality rates rise where physician density
rises.

Neither
the reviewers nor we can ignore the negative
correlations between physician density and noncancer, nonIHD causes of
death, by Census Divisions. To be a "better explanation" for the
observations, a proposition must be consistent with all the key observations.

Critique
#3 cannot explain the noncancer nonIHD observations.
When pressed, one reviewer proposed that only people having cancer and
IHD want to be near doctors, but people having other fatal illnesses do not
feel the same desire. The other reviewer conceded that her proposition
cannot explain all of the key observations.

But
the x-ray explanation can. Cancer and IHD behave
differently with respect to physician density because rising physician
density means rising average accumulated per capita x-ray exposure.
Noncancer causes of death are not known to be inducible by x-rays,
whereas x-rays are a proven human carcinogen (via mutations). So a
different response would be expected, to rising physician density.

As
for IHD, our study provides the first powerful epidemiologic
evidence that x-rays (via mutations) are very probably an atherogen as well
as a carcinogen. Long before 1999, some independent, supplemental
evidence already existed that mutations acquired after conception have a role
in atherogenesis, but we and many others either were unaware of it or paid
it too little attention --- until our 1999 monograph. Some of the
supplemental evidence on IHD is described
in Note 1.

Part 9 Correlations Show Only that People Live Long
Enough to Die of Cancer or IHD Where Doctor Density Is High?

Critique
#4. Two other reviewers proposed, as a "better
explanation" for the positive correlations uncovered in Gofman 1999, that
"With an increased number of physicians per 100,000 population, better
medical care, the population lives longer making death from an age-related
disease (cancer or heart disease) more likely" (Arvid Zuber, Ph.D., April
15, 2000, in a critique sent to the magazine "World and I"). The other
reviewer used different words to convey the same idea.

Our Response: Age-Adjusted Mortality Rates Equalize the
Number of Persons Reaching Each Age

These
two reviewers are thinking of what is called "crude"
mortality rates. But every mortality rate used in Gofman 1999 was an
age-adjusted mortality rate. There is a big difference in their meaning.

By
definition, age-adjusted mortality rates for each of the nine
Census Divisions are adjusted for the same age-distribution, and are
based on the observed age-specific observations of deaths per 100,000
persons in a Census Division who do reach each specific age (sample
calculation shown in Gofman 1999p.87).

These
two reviewers have no explanation for why the cancer and
IHD mortality rates are higher, per 100.000 persons who do reach
advanced ages, where physician density is higher than where it is lower, by
Census Divisions. So they have not identified a "better explanation" than
the higher accumulated per capita dose of x-rays, where physician density
is higher --- as subsequently acknowledged by one of the reviewers who
offered Critique #4.

Part 10 "Ecologic Studies" Are Inherently Weak

Critique
#5. The fact that our study can be labeled "an ecologic
study" helps people to dismiss it (see Part 7,
above). Dr. Colton pointed
out, "You can't say that everybody has been exposed to physicians and
everybody who's had cancer and who's died from cancer has had these
x-rays" (Veterans 2000, p.273).
An ecologic dose-response study leaves open the possibility that
the response is coming from people who received no dose.

Our Response: By 1940, Nearly Everyone Was X-ray Exposed

While
few people have x-rays every year, what counts is the
accumulated dose. The mutations accumulate. The body remembers.

X-rays
("roentgen rays") were discovered in December 1895,
and were introduced so rapidly into medicine that until about 1906, x-rays
"were tried out [as therapy] on nearly every chronic disease"
(MacKee 1938 pp.15-16).
After World War One, a radiologist commented to his
colleagues about "the large number of internists who have placed
fluoroscopes in their offices, not with the idea of specializing in the work,
but simply wishing to have conveniently at hand an x-ray control of their
physical findings ... The simplified apparatus which has developed from
war-time [battlefield] practice is conspicuous"
(Hickey 1923).
"Fluoroscopy, I venture to assert, will become a routine measure in every
physician's office before very long" (Bishop 1922).

And
so it came to pass that, in 1937, Dr. Eugene Leddy of the
Mayo Clinic wrote: "Roentgenologic methods of diagnosis are so important
that no investigation of a patient is considered complete without
roentgenologic examinations, which generally include roentgenoscopy
[fluoroscopy]" (Leddy 1937 p.924).
One expert has estimated that the average x-ray dose per fluoroscopy
was 65 rads (Moeller 1953, p.58-59).

We
consider it highly unlikely that in the United States, more
than a very small share of people dying in 1940, of any illness, escaped
x-ray exposure during their lifetimes.

Part 11 Is It "Impossible" for X-Rays to Be a Necessary
Causal Co-Actor in Over Half the Cancer and IHD Mortality?

Critique
#6 was presented, separately, by two health physicists:
By Dr. Roland Finston, orally at a breast cancer forum (2001), and by Dr.
Brian Wowk in the magazine, "Life Extension"
(Wowk 2002 p.75).

Their
critique asserts that our conclusion, that x-rays are a
necessary causal co-actor in over half the cancer and IHD mortality, cannot
be correct because the average annual radiation dose from natural
background radiation is about 6 times higher than the average annual
accumulated dose from medical x-rays. Therefore, even if ionizing
radiation were a necessary causal co-actor in every fatal case of cancer and
IHD, x-rays could contribute only a small share compared with natural
background radiation.

Our Response: The Dose-Ratio Deserves Reversal

Dr.
Wowk accepts the common estimate that annual per capita
dose from medical imaging is, today, about 0.05 rem or centi-sievert
(cSv), as does Dr. Finston. They just ignore the fact that this is necessarily
a "thin air" estimate (Part 3,
above). The "thin air" estimate does not even
approach the status of a scientifically incontrovertible fact. Therefore, our
conclusion is certainly not invalidated just by being incompatible with the
0.05 rem estimate.

These
reviewers, in addition, say nothing at all about average per
capita past doses, which are the relevant ones, here. Our study begins
with the 1940 mortality rates, for which the x-ray doses accumulated
between 1900 and 1940 are the only ones which matter.

In
Appendix K of Gofman 1999,
we explored this issue by trying
to make an estimate of what the annual per capita x-ray dose may have
been prior to 1940. Using papers by Donaldson (1951)
and Moeller (1953),
plus clearly stated assumptions and logic, we estimate that the
average annual per capita whole-body dose from medical imaging in 1950
was in the region of 0.65 rad, excluding non-imaging (therapeutic) uses of
x-rays, radium, and excluding all dental x-rays. We challenge anyone to
show that some lower estimate for midcentury is more credible than 0.65
rad.

Indeed,
0.65 rad is likely to be quite an underestimate, because of
all the x-ray procedures it omits. It properly omits uses for cancer therapy
(because we are investigating cancer causation). But 0.65 rad also excludes
numerous x-ray therapies for "benign" noncancer ailments, including 80
skin disorders (cumulative doses of many hundred rads per treatment),
enlarged thymus gland, mastitis, tuberculosis, asthma, pneumonia,
tendonitis, certain kinds of pain, and more
(see MacKee 1938,
Gofman 1996).

"It
has been said that radiation therapy has been used
promiscuously, on every disease there is, and probably so," wrote the
radiologist, Stephen B. Dewing (Dewing 1965 p.ix).

Comparing Two Kinds of Doses: X-Rays and Natural Background

A
medical rad is not directly comparable with the estimated
average annual whole-body dose of 0.3 rem or cSv from natural
background radiation. Evidence from radiation track analysis indicates that
a reasonable conversion factor, from rads to rems for medical x-rays, is
about 1.7 (see tabulation, text, and references
in Gofman 1999p.47).

Multiplication
of 0.65 rad (medical) times 1.7 rem per rad yields
1.1 rem as a credible estimate of the average annual per capita whole-body
dose from medical x-rays during the first half of the 20th century. It
compares with an average dose of only 0.3 rem from natural background,
including 0.2 rem from radon (BEIR 1990
p.18). The 0.3 rem estimate (natural) is itself a very uncertain
estimate, strongly affected by several key assumptions. Nonetheless,
we will use it.

These
two values (1.1 rem, medical, and 0.3 rem, natural) mean
that the annual per capita whole-body dose at midcentury from x-rays
could easily have been about 3.7 times higher than the dose from natural
sources (1.1 / 0.3).

This
is quite a reversal of the ratio assumed by the two
reviewers.

Even
though we assume that average per capita x-ray doses are
no longer as high as the midcentury estimate, we are mindful that x-ray
practices in 1950 affect cancer and IHD mortality rates for the subsequent
50 years and probably longer --- by producing some carcinogenic and
atherogenic mutations which endure (Part 3, above).

Fortunately,
after 1955 or so, radiation has been seldom used
therapeutically, except for cancer therapy. On the other hand, two large
upward forces on average per capita x-ray dose have been introduced
during the 1970-2000 period. Uses of fluoroscopy --- delivering x-rays
at 2 to 20 rads per minute --- have greatly expanded, e.g., during
catheterizations, surgeries, and other common procedures
(Gofman 1996).
Another large upward force on average per capita x-ray dose is the
replacement of many "planar" x-ray images by CT procedures during the
1980-2000 period (see Part 3, above).

In
summary, nothing in Critique #6 invalidates the conclusions of
Gofman 1999, that medical x-rays were and remain a necessary co-actor in
over half the U.S. mortality rates from cancer and IHD.

Part 12 Conclusion: A Biologically Consistent Picture

We
have studied the relationship of age-adjusted mortality rates
and physician density with 40 separate tests
(Part 4, above). The findings
sort themselves out in a biologically consistent way, almost without
exception (Part 5,
above). Such correlations do not happen just by
accident. Moreover, they have happened in the way one would expect,
if medical x-rays are the cause.

No
critique thus far of the findings, concerning medical x-rays in
the causation of cancer and coronary artery disease, provides a better
explanation of all the observations in
Gofman 1999, and no critique shows
that the new conclusions are "impossible" due to any contradiction of a
scientifically incontrovertible fact.

At
issue is prevention of some 250,000 premature deaths per year
in the USA, by cutting average per capita x-ray
exposure in half (Part 1, above). Does
this not suggest that the medical profession needs to use
more speed in taking the findings seriously?

# # # # #

NOTE 1.
Some Supplemental Evidence for Atherogenic Mutations

Human
Pathologic Evidence. In 1973, Earl Benditt and
co-workers reported that human atherosclerotic plaques were far more
monoclonal than adjacent non-atherosclerotic tissue
(summary in Gofman 1999
Chapter 44). Others confirmed those pathologic observations. Do
those findings indicate that such plaques arise due to mini-tumors?
Research on the cause of such monoclonality continues at the University of
Washington Pathology Department.

Experimental
Animal Studies. In 1977, Roy Albert and
co-workers published evidence
that weekly injections of strong chemical
carcinogens "resulted in large, proliferating plaques in the abdominal aorta
in cockerels" (from Penn 1989
p.190). Penn himself showed, in a series of
papers (1981, 1986, 1988, 1989, 1991), that DNA from the coronary artery
plaques of some human patients can transform NIH 3T3 fibroblasts, which
thereby acquire the power to produce tumors in nude mice, and that
injection of experimental animals with a variety of established chemical
carcinogens and mutagens promotes expansion of arterial plaques in such
animals. See Penn 1990
and Gofman 1999 Chapter 44.

Ionizing
radiation at high therapeutic doses has also been explored
as an atherogen in nonhumans. In 1976, Richard A. McReynolds et al
summarized evidence as follows: "When irradiation is given to animals
(rabbits or rats) on high cholesterol diets, severe coronary atherosclerosis
results, far more severe degrees of atherosclerosis than that resulting from
the hypercholesterolemia alone. Irradiation and hypercholesterolemia
appear to act synergistically to produce considerably more atherosclerosis
than that produced by either radiation or hypercholesterolemia alone"
(McReynolds 1976 pp.44-45).

Atherogenic Mutations as a Necessary Co-Actor in IHD Deaths

Our
"Unified Model" (Gofman 1999 Chapters 45, 46) builds
upon prior evidence that a major cause of heart attack is the rupture in a
coronary artery of an atherosclerotic plaque's fibrous cap, whose rupture
releases the plaque's thrombogenic lipid pool into the bloodstream.

Our
Unified Model proposes that a lipid-containing arterial
plaque arises where mutations (acquired after conception) produce a clone
of dysfunctional cells (mini-tumors) which do an incomplete job of clearing
the lipids out of that patch of dysfunctional tissue and of protecting the
arterial lumen from the accumulated lipids therein. This model is consistent
not only with previously established risk factors for IHD, but it also
explains why plaques occur only in discrete patches, surrounded by normal
tissue.

AMA. The American Medical Assn. has collected and published
data on physician density since the early 20th century. The AMA data are
used by the U.S. Public Health Service for its own publications (e.g.,
Pennell 1952). For the second half of the
20th century, Gofman 1999 used the AMA's 1982,
1985, 1994 editions of Physician Characteristics &
Distribution in the U.S.

Hickey 1923 (Preston),"The Effect of the War on the
Development of Roentgenology," Amer. J. Roentgenology 10: 70-75.

IARC 2000 (Internatl. Agency for Research on Cancer, of the
World Health Org.), IARC Monographs on the Evaluation of Carcinogenic
Risks to Humans, Vol.75, Ionizing Radiation, Part 1: X- and
Gamma-Radiation. ISBN 9283212754.

Natl Center (Natl Center for Health Statistics). The NCHS,
located in Hyattsville, Maryland, is now a subdivision of the U.S. Centers
for Disease Control. Its branch for Vital Statistics, Mortality, supplied the
1980 and 1993 age-adjusted mortality rates presented in
Gofman 1999 for
the nine Census Divisions. Details in Gofman 1999
p.79.

Veterans 2000 (U.S. Dept. of Veterans Affairs, Office of
Adjudication, Veterans' Advisory Com'tee on Envir. Hazards). This
committee met in Washington DC on Nov. 29, 2000. A transcript of the
discussion was made by the Miller Reporting Company. The Department
supplied a copy to Dr. Gofman at his request.